The proposed research is concerned with the mechanism of DNA replication. The approach will be three-fold. First, we are continuing to investigate the mode of action of the drug and DNA synthesis inhibitor, nalidixic acid. Second, we are studying nascent DNA chains, the so-called Okazaki pieces. We are focusing on their initiation, synthesis, and structure. Third, we are just beginning a study of DNA replication in vaccinia virus, a large virus which replicates in the cytoplasm.